1. Field of Invention
The present invention relates to a new process for the preparation of certain known aryl-pyrido[1,4]benzodiazepines from pyridobenzodiazepinones and novel chemical intermediates involved therein.
2. Information Disclosure Statement
Certain of the aryl-pyrido[1,4]-benzodiazepines preparable by the process of the present invention and having aminoalkyl substitution on the solitary bridging nitrogen are disclosed in U.S. Pat. No. 4,447,361, the specification of which is hereby incorporated by reference to show in particular the formula numbering system used herein for compounds having varying pyridine nitrogen position. In the method of preparation disclosed in that patent, amino-halopyridine and aminoarylphenones were heated neat to give pyrido[1,4]benzodiazepines.
U.S. Pat. No. 4,560,510 discloses utilization of a strong non-nucleophilic base to bring about condensation of an aminochloropyridine and an aryl(aminophenyl)methanone in admixture with mobile inert carrier to produce pyrido[1,4]benzodiazepines. Preparation of pyrido[1,4]benzodiazepines of the present invention by that method having a ##STR3## radical on the solitary bridging nitrogen atom and utility thereof in preparing the corresponding aminoalkyl-N-substituted compounds is disclosed therein.
U.S. Pat. No. 4,480,100 describes preparation of certain of the subject aryl-pyrido[1,4]benzodiazepines by cyclizing [2-[(aminopyridinyl)amino]phenyl]arylmethanones, the latter having been prepared from a nitro intermediate.
U.S. Pat. No. 4,558,132 describes preparation of aryl-pyrido[1,4]benzodiazepines by cyclizing aroylamino-N-phenylpyridineamines.
British Patent No. 1,456,627 and U.S. Pat. No. 4,021,557 disclose preparation of pyrido[2,3-b][1,4]benzodiazepinone having the formula: ##STR4## which is a precursor to starting compounds for the instant process. Aminoalkyl substitution on the solitary bridging nitrogen at the same time the other azepine nitrogen is substituted by a methyl group is also disclosed.
The procedure used in the instant process to acylate the unsubstituted nitrogen of N-substituted-pyridobenzodiazepinones in the initial step of the instant process and the subsequent reaction with Grignard reagent has similarity to that described by Gates, M. in J. ORG. CHEM. 45, 1675-1681 (1980) for synthesis of diazepam.